1. Field of the Invention
This invention relates to the field of monitoring the amount of analyte, e.g., glucose, cholesterol, in body fluid. More particularly, this invention provides an article and method that monitors the amount of analyte in body fluid by means of a test that employs only a small volume of biological fluid.
2. Discussion of the Art
The prevalence of diabetes has been increasing markedly in the world. At this time, diagnosed diabetics represented about 3% of the population of the United States. It is believed that the total actual number of diabetics in the United States is over 16,000,000. Diabetes can lead to numerous complications, such as, for example, retinopathy, nephropathy, and neuropathy.
The most important factor for reducing diabetes-associated complications is the maintenance of an appropriate level of glucose in the blood stream. The maintenance of the appropriate level of glucose in the blood stream may prevent and even reverse many of the effects of diabetes.
Glucose monitoring devices of the prior art have operated on the principle of taking blood from an individual by a variety of methods, such as by needle or lancet. An individual then coats a paper strip carrying chemistry with the blood, and finally insert the blood-coated strip into a blood glucose meter for measurement of glucose concentration by determination of change in reflectance.
There are numerous devices currently available for diabetics to monitor the level of blood glucose. The best of these devices require the diabetic to prick a finger and to collect a drop of blood for placement on a strip, which is inserted into a monitor that determines the level of glucose in the blood. Pricking one's finger tends to be painful. Moreover, a relatively large wound is produced by the pricking device, typically a lancet or a needle. It is known that the pain arising from the finger prick deters diabetics from compliance with the monitoring regimen. Lack of compliance increases the risk of complications due to diabetes. Thus there is a need for a more painless and less traumatic means of collecting biological samples for monitoring one's level of glucose in blood.
Several patents have. proposed that the level of glucose in blood can be monitored by measuring the level of glucose in interstitial fluid. In order to obtain samples of interstitial fluid, the barrier function of the stratum corneum must be overcome. Jacques, U.S. Pat. No. 4,775,361, discloses a method of ablating the stratum corneum of a region of the skin of a patient by using pulsed laser light of a wavelength, pulse length, pulse energy, pulse number, and pulse repetition rate sufficient to ablate the stratum corneum without significantly damaging the underlying epidermis. This patent discloses the use of laser light having a wavelength of 193 nm or 2940 nm. Laser light having wavelengths of 193 nm or 2940 nm can be provided by an excimer or Er:YAG light source, respectively, both of which are extremely expensive.
Tankovich, U.S. Pat. No. 5,423,803, discloses a process for the removal of superficial epidermal skin cells in the human skin. A contaminant having a high absorption in at least one wavelength of light is topically applied to the surface of the skin. Some of the contaminant is forced to infiltrate into spaces between superficial epidermal cells. The skin section is illuminated with short laser pulses, with at least at least one of the pulses having sufficient energy to cause some of the particles to explode tearing off the superficial epidermal cells.
Zahrov, WO 94/09713, discloses a method for perforating skin comprising the steps of (a) focusing a laser beam in the shape of an ellipse at the surface of the skin with sufficient energy density to create a hole at least as deep as the keratin layer and at most as deep as the capillary layer; and (b) creating at least one hole, each hole having a width between 0.05 and 0.5 mm and a length of equal to or less than 2.5 mm.
It should be noted that it is desirable for a diagnostic device for monitoring glucose provide a result rapidly. Most commercially available devices provide a result in under one minute. This one-minute period runs from the moment of sticking the finger to the display of the result on a meter. When interstitial fluid is used as the sample, the goal of a one-minute testing period is difficult to satisfy, because the methods for obtaining interstitial fluid typically provide samples of less than 1 .mu.L per minute. In order to determine the quantity of glucose in a sample of interstitial fluid, sensitive detection methods must be employed. It is well known that a common method for increasing assay sensitivity is to increase the size of the biological sample. However, increasing the size of a sample of some biological fluids, such as interstitial fluid, has been found to be difficult.
U.S. Pat. Nos. 5,161,532; 5,508,200; 5,202,261 disclose the use of biological fluids to determine the concentration of glucose in the blood. U.S. Pat. No. 5,161,532 discloses an interstitial fluid sensor. The sensor is applied to the skin of a person or animal to detect the chemical components of the interstitial fluid. The sensor comprises a substrate of porous material, which permits the passage of the interstitial fluid therethrough. At least two electrodes are provided. One of the electrodes has two sides, with one side mounted on the substrate. The one electrode is also of a porous material for the passage of the interstitial fluid from the one side in contact with the substrate to through to the second side, which is generally opposite the one side. A layer of chemical is on the second side. The layer comprises a chemical for reaction with one component in the interstitial fluid. The chemical is mixed in a mediating agent. The electrodes produce a response to the reaction of one component of the interstitial fluid with the chemical. A detector receives the electrical signal; generated by the electrodes and generates a display indicative of the amount of the one component in the interstitial fluid. According to this patent, at a sampling rate of approximately 0.4 microliter/min/cm.sup.2, the entire electrodes can be wetted in less than 2 seconds.
U.S. Pat. No. 5,508,200 discloses a system for high performance automated chemical analysis including a video camera photometer with a computer-controlled interference filter wheel. A fluidics system delivers ultramicro sample and reagent volumes in the 0.05 to 5.0 microliter range to a supporting analytical media. The media is precisely positioned relative to the photometer by an x-y axis reaction media holder capable of accurate and precise position of the ultramicro reaction spots. The reaction media can consist of absorbent cellulose sample/reaction strips or microscopic sized multiple wells. A data and reduction system monitors multiple simultaneous reactions within a common test area of the analytical media to provide final quantitative reports. The method for conducting multiple chemical assays involves placing small volumes of sample/reagent combinations at discrete locations about a common test area on the analytical media and simultaneously measuring resulting optical changes at each discrete location.
U.S. Pat. No. 5,202,261 discloses a diagnostic device including a conductive analyte sensor comprising a reaction zone and a detection zone, wherein the detection zone includes a conducting polymer and a microelectrode assembly. The conductive sensor allows the detection and measurement of a predetermined analyte in a liquid test sample, wherein the predetermined analyte is assayed by an oxidase interaction. An interaction between the predetermined analyte and an oxidase enzyme occurs in the reaction zone of the conductive sensor to produce, either directly or indirectly, a dopant compound that migrates to the detection zone of the sensor. The detection zone of the device is in laminar contact with the reaction zone and includes a layer or film of conducting polymer that is oxidized by the dopant compound. Therefore, the conductivity of the conducting polymer is changed, and the change in conductivity of the conducting polymer layer is detected and measured by the microelectrode assembly and is correlated to the concentration of predetermined analyte in the sample. The device can utilize a test sample having a volume of from about 0.1 .mu.L to about 5 .mu.L, and usually less than 1 .mu.L of whole blood.
It would be desirable to provide a means for detecting the concentration of glucose in small volumes of interstitial fluid, preferably with an optical reading system, because such a system is more sensitive than an electrochemical reading system.